This invention relates to a method of operating a mass spectrometer to suppress unwanted ions.
Collision cells are widely used for Collision Induced Dissociation (CID) of precursor ions in Mass Spectrometry. Usually, the product ions of the desired CID are intended to be conducted efficiently to the next stage of a tandem mass spectrometer in order to be mass-analyzed and detected. However, many unintended or undesired processes can occur in the collision cell, producing undesirable ions, for example, cluster ions, or un-specific fragment ions that elevate chemical background and decrease signal-to-noise ratio for the ions of interest measured by a downstream mass analyzer.
Reaction/collision cells are commonly used in Inductively Coupled Plasma Mass Spectrometry for suppression of unwanted ions originating from the ion source, which often is an Argon inductively coupled plasma source (Ar ICP). For example, Ar+, ArO+, Ar2+, ClO+ etc. are generated in Ar ICP. In such cells, together with xe2x80x9cusefulxe2x80x9d reactions that suppress interfering ions, other reactions can take place, for example, cluster formation, atom-transfer reactions, and condensation reactions that produce xe2x80x9cundesirablexe2x80x9d product ions that elevate background at the mass of interest measured by downstream analyzer. Generally these reactions can reduce signal-to-background ratio.
There are also collision cells in Mass Spectrometry that are used only as transmission devices, that utilize collisional focusing, to achieve spatial focusing or temporal beam homogenization. In such cells any reactions are often un-desirable, and product ions of such reactions decrease the performance of the mass spectrometer due either to elevation of the background at the mass of interest, or to loss of the analyte signal due to the reaction. U.S. Pat. No. 4,963,736 discloses such a technique sometimes identified as collisional focusing.
To date, there are three known ways to control the products of undesirable reactions in such pressurized reaction/collision cells.
One way is to accelerate ions while they are transported through the pressurized device in order to reduce the residence time and/or increase the ion velocity between the collisions so that undesirable reactions"" cross-sections are reduced. This is achieved by application of the axial internal field and is described in the patent U.S. Pat. No. 5,847,386 by Bruce A. Thomson and Charles L. Jolliffe, and assigned to MDS Inc. (the assignee of the present invention). This ion acceleration method does suppress cluster ion formation, but other reactions (for example, atom-transfer) are not intercepted, and, in fact, some endothermic reactions can be promoted by supplying through the axial internal field some additional energy to the collision complex.
A second way is to prevent formation of undesirable product ions by making the parent or intermediate product ions unstable in the rf-quadrupolar field of the pressurized cell, as described in the patent U.S. Pat. No. 6,140,638 by Scott D. Tanner and Vladimir I. Baranov (also assigned to the assignee of the present invention). By changing the parameters of the quadrupole (a and q), the range of ion masses that are unstable in the cell can be changed. As unstable ions are ejected from the cell, they do not contribute to the undesirable product ion formation. The approach has proven itself very successful in intercepting unwanted sequential chemistry in the Inductively Coupled Plasma Dynamic Reaction Cell Mass Spectrometry (ICP DRC(trademark) MS), (DRC is a trade mark of the assignee of the present invention). The highest efficiency achieved to date in ICP DRC MS has given 9 orders of magnitude of suppression of unwanted Ar+ without significant suppression of analyte ions, by charge-exchange with NH3, and this is done without significant elevation of chemical background. The approach works well when the analyte and the unwanted precursor ion have a relatively large difference in mass, so that the unwanted precursor ion can be efficiently removed without significant suppression of the desired analyte. A typical example of the method is detection of 52Cr+ which can suffer interference by (NH3)3H+ for a cell pressurized with NH3, where the primary precursor ion of the interfering cluster ion is NH4+ (m/z=18). When the signal at m/z=52 is measured at q (m/z=52)=0.4, the precursor ion (NH4+) that forms the interfering cluster ion, is unstable in the quadrupole field, as its stability parameter q, which is inversely proportional to the ion mass, is       q    m1    =                    q        m2            xc3x97              m2        m1              =                  0.4        xc3x97                  52          18                    =      1.2      
which is outside of the stability boundary.
However, if the relative difference between the undesired product ion mass and the unwanted precursor ion mass is low, as, for example, between product CeO+ at m/z=156 and the precursor 140Ce +, then measurement of a desired analyte 156Gd+, likely to suffer interference from CeO+, may require q=0.82 in order for 140C e+ to be unstable in the quadrupole. Such a high q will cause significant suppression of the 156Gd+ signal.
A third way of discriminating against unwanted product ions is by applying kinetic discrimination downstream of the pressurized cell, as described by J. T. Rowan and R. S. Houk in their paper xe2x80x9cAttenuation of Polyatomic Ion Interferences in Inductively Coupled Plasma Mass Spectrometry by Gas-Phase Collisionsxe2x80x9d, Applied Spectroscopy, 1989, 43,976. This approach works best for the cells pressurized to a relatively low pressure. Ions that are produced in the cell, including undesirable product ions, have somewhat lower kinetic energy after leaving the cell, than the ions desired for detection (analyte ions) that retain some of the kinetic energy with which they entered the cell, provided there are not enough collisions to smear the difference in energy by collisional energy damping. This approach cannot be successfully used if, for high efficiency of the desired reaction, a high number of collisions and thus high gas pressure are required.
The present invention provides a fourth, novel and inventive way to discriminate against product ions produced in a pressurized device, by applying an energy discrimination principle continuously during the ion transport through the cell. The invention provides a retarding field inside the cell, so that the product ions are discriminated against after each collision, i.e. immediately after they are formed and before their energy is damped by further collisions. There are at least two xe2x80x9ctypesxe2x80x9d of unwanted ions that the invention may help to alleviate. First, ions that are produced within the cell and may interfere with the determination of an analyte ion. Second, polyatomic ions that may be produced in the cell or may be sampled from the ion source and that may interfere with the determination of an analyte ion. In either instance, the impact of the retarding internal field has a similar effect, but we will discuss them separately as the polyatomic ion alleviation has some special characteristics. Relative to the initial energy of the ions as they enter the cell, the neutral gas molecules within the cell may normally be considered stagnant. Ions, both wanted and unwanted, lose kinetic energy in collision with the neutral gas molecules. Ions that are transformed by the exchange of a particle (electron, atom or ligand), and hence may form a new isobaric interference for an analyte ion, will tend to have less kinetic energy than an atomic ion which collides without chemical transformation. This is because at least a part of the transformed ion is derived from the stagnant neutral molecule.
In the special instance of polyatomic ions, either produced by reaction within the cell or sampled from the source, some of the energy that is delivered to a collision complex from the ion""s pre-collision kinetic energy can be distributed into the internal degrees of freedom of the product (or original ion that has undergone collision without reaction) polyatomic ion. As a result, its post-collision kinetic energy can be lower than the kinetic energy of an atomic ion of the same mass to charge ratio. Moreover, the polyatomic ions due to their relatively large size may have significantly larger collision cross-sections than that of atomic ions. As a result, they would experience a larger number of collisions and thus would on average lose more kinetic energy per unit length than atomic ions would. The present invention provides a relatively low kinetic energy barrier applied as a continuous field that decelerates the ions and that appears as a kinetic energy barrier to ions whose energies after collision are sufficiently low. Since the undesired product ions and some polyatomic ions, have lower energies after collision than do desired analyte ions, there is a higher probability of the undesired ions being discriminated against, while un-reacted analyte ions can still penetrate through the energy barrier. According to the present invention in which the collisions happen in a retarding internal field, ions that have less energy following collision necessarily have lower transmission to the downstream analyzer when compared to the analyte ions.
Thus, in accordance with the present invention, there is provided a method of operating a mass spectrometer system including a processing section having an input and an output, the method comprising:
a) providing a stream of ions to the input of the processing section defining a path for travel of ions and including means for guiding ions along the path;
b) passing the stream of ions through the processing section which is operated under conditions enabling collisions of ions with neutral particles;
c) providing an internal field extending along at least part of the path of the processing section, to retard movement of ions through the processing section; and
d) selecting the internal field to provide significantly greater retardation to unwanted ions having lower kinetic energy than desired analyte ions, thereby to promote retardation of said unwanted ions and preferential loss of said unwanted ions and to enhance the ratio of said analyte ions to said unwanted ions.
Preferably, the invention includes detecting ions exiting from the processing section. However, it is possible that the ions could be subject to some additional processing, e.g. steps of fragmentation, reaction and/or mass selection, prior to final detection.
The unwanted ions could come from a variety of sources. Generally, the unwanted interfering ions can be ions originating from the ion source, product ions formed by reaction with gas particles in the cell, or ions produced by other processes within the cell. It is also expected that in most cases, the kinetic energy differential between unwanted, interfering ions and desired, analyte ions will result from collision processes in the cell. However, it is possible that unwanted ions could enter the cell with a lower kinetic energy than the desired ions, or at least part of the energy differential will be present when ions enter the cell.